We have identified genes that code for specific rotaviral functions such as neutralization, hemagglutination, growth restriction and protease enhanced infectivity. The general approach involves identification of reproducible differences between two rotaviral strains with respect to one or more such functions. Reassortant viruses are generated by coinfection of cell cultures and then analyzed for functional differences that correlate with specific viral genes. This approach takes advantage of the segmented rotaviral genome that allows reassortment to occur during coinfection. Genetic analysis of the reassortants by polyacrylamide gel electrophoresis (PAGE) permitted us to identify the parental origin of each gene. Using this approach we demonstrated that the 8th or 9th gene (depending on the strain) of human rotavirus codes for the neutralization antigen and that the 6th genomic segment codes for the subgroup antigen. Recently we have identified the 4th RNA segment as coding for rotaviral hemagglutinin. This protein is activated by a protease and such activation is required for virus to be infectious. Thus the ability of rotaviruses to infect cells is multigenic involving the products of at least two different genes.